CStone showcases robust preclinical results for three proprietary ADCs at AACR 2026; IND filings slated for 2026

Bulletin Express
04/20

CStone Pharmaceuticals (CStone) presented comprehensive preclinical data for three antibody-drug conjugates (ADCs)—CS5007 (EGFR/HER3 bispecific), CS5006 (ITGB4-targeting) and CS5008 (DLL3/SSTR2 bispecific)—during the American Association for Cancer Research Annual Meeting (17-22 April 2026). All three candidates are derived from the company’s in-house CSL20 linker–exatecan platform, designed for high plasma stability (<0.6 % free payload at day 7) and potent by-stander-effective payload release.

CS5007 (EGFR/HER3 ADC) • Molecular stability: <0.5 % payload release after 7 days, surpassing the trastuzumab deruxtecan benchmark. • Dual-pathway blockade: The antibody J17 inhibited both Akt and MAPK signaling in multiple EGFR/HER3-positive cell lines, outperforming SI-B001. • Anti-tumour activity: Nanomolar-range cytotoxicity across NSCLC, SCC, CRC, PANC and breast models; pronounced by-stander kill of antigen-negative cells in co-culture. • In vivo efficacy: Tumour regression in CDX models, including osimertinib-resistant H1975 (C797S) and low-EGFR/high-HER3 SW620 models, where comparator BL-B01D1 was inactive. • PK/PD & safety: Half-life ~20 h (vs. ~10 h for BL-B01D1) and highest non-severe toxic dose (HNSTD) 30 mg/kg in GLP studies; no lethal toxicity observed. • Development plan: IND submission targeted for 1H 2026; first-in-human monotherapy dose-escalation/expansion study (≈70 patients with advanced solid tumours) planned.

CS5006 (ITGB4 ADC) • Target rationale: ITGB4 is overexpressed in CRC, NSCLC, HNSCC and ESCC, with limited normal-tissue expression. • Molecular stability: <0.6 % payload release after 7 days in human or monkey serum. • Cellular performance: Rapid internalisation and nanomolar antigen-dependent cytotoxicity; potency correlated with ITGB4 surface density and demonstrated by-stander killing via released payload. • Xenograft data: Broad tumour growth inhibition across NSCLC, breast, CRC, SCCHN, urothelial, ESCC and gastric models. • PK & safety: Half-life ~3.5 days and provisional HNSTD 45 mg/kg in non-human primates. • Development plan: IND filing expected in 2H 2026.

CS5008 (DLL3/SSTR2 bispecific ADC) • Rationale: DLL3 and SSTR2 are overexpressed in >70 % of small cell lung cancer (SCLC) and neuroendocrine tumours; dual targeting aims to mitigate intratumoural heterogeneity and subtype switching. • Serum stability: <0.5 % toxin release after 7 days in human and monkey serum. • Cellular activity: Rapid, antigen-dependent internalisation; cytotoxicity proportional to combined DLL3/SSTR2 expression. • In vivo efficacy: Single-dose treatment induced regression in diverse SCLC models, including DLL3-negative H446, outperforming mono-specific comparators. • PK & safety: Half-life ~14 days; provisional HNSTD 60 mg/kg in cynomolgus monkeys, no lethal toxicity. • Development plan: IND submission planned for 2H 2026.

Strategic context Founded in 2015, CStone has four commercialised drugs and 21 approved indications. Its 16-asset pipeline emphasises ADCs, multispecific antibodies and precision medicines. The disclosed preclinical data reinforce the company’s expansion into next-generation ADCs targeting high-unmet-need solid tumours and support upcoming clinical trial applications across 2026.

Shareholders are reminded that CS5007, CS5006 and CS5008 remain in preclinical development; regulatory approval and commercialisation are not assured.

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